ANS reversal agents Flashcards
what converts dopamine to NE
dopamine beta hyroxylase
how is norepinephrine metabolized
reuptake (70%), the rest metabolized by monamine oxidase (MAO) and catecholomethyltranserase (COMT)
the alpha 1 receptor is ____synaptic
post
alpha 1 works in the
periphery
alpha 2 receptor is ___synaptic
pre
beta 1 receptor is in the
heart
beta 2 is in the
other smooth muscle
activation of alpha 1 increases
intracellular calcium
alpha 1 causes smooth muscle ___ and peripheral vaso___
contraction, vasoconstriction
which anticholinergics are tertiary amines
atropine and scopolamne
which anticholinergics are quaternary ammonium
glycopyrrolate
electrostatic attachment occurs with
edrophonium (competitive)
formation of caramyl esters occurs with
neo, phyido, physo (competitive)
phosphorylation occurs with
organophosphates and echothiophate (non-competitive inhibition)
how do AchE inhibitors work
they reversibly inhibit AchE, which indirectly increases the concentration of Ach at the neuromuscular junction. since more ach is present, it is better able to compete for the alpha binding sites on the nicotinic receptor and antagonize the block
neostigmine is ___ potent than pyridostigmine
more
50% of ___ is metabolized by the liver
neostigmine
which drugs are quaternary amines
endro, neo, phyrido
quaternary pass thru BBB?
no
tertiary amine pass thru BBB?
yes!
which is tertiary amine
physostigmine
AchE inhibitors cause ____ side effects
parasympathetic
why do AchE inhibitors cause cholinergic side effects
because there is more ach at the muscarinic receptor.
cholinergic side effects are
diarrhea , urination, miosis, bradycardia, bronchoconstriction, emesis, lacrimation, laxation, salivation
whats the only AchE inhibitor that diffuses across BBB
physostigmine
whats the best AchE inhibitor to antagonize a block with 90% twitch suppression
neo
which drugs produce reversible inhibition of AcheE by forming a caramel ester complex at the esteratic site… block the enzymes ability to hydrolyze Ache
neo and pyrido and pyrido
which enzyme forms a reversible electrostatic attachment
edro
neo edro pyrido. which is most potent
neo
neo edro pyrido. which is least potent
edro
which drugs prolong the duration of succs
neo and pyrido
pyrido edro neo . which has fastest onset
endro
pyrido edro neo which has slowest onset
pyrido
atropine can be mixed with
edro
glyco can be mixed with
neostigmine
glyco and edro in the same syringe will cause profound
bradycardia (same with administering atropine after edro)
Atropine and scopolamine structure
tertiary amines, liophillic
glyco structure
quaternary ammonium, does not pass thru lipophilic membranes
sugammadex affinity for amino steroids > > >
rec>vec>panc
which drug competitive inhibition, electrostatic attachment
edro
metabolism of edro and pyrido
75% renal, 25% hepatic
metabolism of neo
50% renal, 50% hepatic
neostigmine is ___ in infants and children
faster
which antimuscarinics pass thru BBB
atropine and scop
roc metabolism
primary biliary
sugmmadex metabolism
excreted unchanged by kidneys
SNS stim effect on bronchial smooth muscle
relaxation
PNS stim effect on bronchial smooth muscle
contraction
PNS stim effect on gallbladder
contraction
PNS stim effect on urinary
smooth muscle contraction, sphincter relaxation
PNS stim on GI tract
inc motility, secretion, sphincter relaxation
SNS stim on liver
glycogenolysis
PSN stim on liver
glycogen synthesis
SNS stim on eye
mydriasis
pNS stim on eye
miosis
SNS stim on pancreas
dec beta cell secretion
down regulation
extended exposure to agonists reduces the number, but not their response. results in tachyphylaxis
up regulation
chronic depletion of catecholamines or use of antagonists increases the number of receptors but not their sensitivity. may account for withdrawal syndrome with BB
receptor uncoupling occurs ___, while sequestration occurs ___
rapidly, slowly
pheochromocytoma
renal tumor. uncontrolled release of catecholamines due to an adrenal gland tumor. constant SNS stimulation. pump out epi and norepinephrine constantly.
sympathomimetics
compounds that resemble catecholamines except that hydroxyl groups are not present in both the 3 and 4 positions of the benzene ring
where is epi released from
adrenal medulla , triggered by calcium ion influx
presynaptic effect we would see with AchE inhibitor?
fasciculation at high doses
direct effect of anti cholinesterase ?
super high dose causes NMB blockade
what is the most important determinant of relative potency ?
affinity
influence of age with neo
infants
edrophonium and age
no change
nicotinic effects occur at
NM junction and autonomic ganglia
muscarinic effects include
bradycardia, salivation, bronchoconstriction, miosis, hyperperistalsis, and increased risk of PONV
eye effects from anti cholinesterase
miosis, inability to focus on near vision, dec IOP
pulm effects from anti cholinesterase
bronchoconstriction, increased airway resistance
how are anti cholinesterase used to tx myasthenia graves?
increase ACh at the nmj
potency of anti cholinesterase is determined by
NMB being antagonized, speed of spontaneous recovery, and depth of NMB when reversal is initiated
whats the purpose of an anticholinergic drug
blocks the side effects of the muscarinic receptors
administer reversal only after twitch height has recovered to
> 10%
what can prevent you from properly reversing someone?
abx, hypothermia, resp acidosis, hypoK, metabolic acidosis
physostigmine CNS effects
antagonizes adverse CNS effects of certain drugs
which drug decreases post-op somnolence after volatile anesthetic and reverses CNS effects of ketamine
physo
which drug is used for post op analgesia and post op shivering
physo
which drug is used for diagnosis and management of cv arrhythmias
physo
most two significant OD muscarinic effects
bronchoconstriction and bradycardia
OD nicotinic effects
skeletal muscle weakness to paralysis and apnea
organophsphate anticholinesterases
insecticides and nerve agents - rapidly absorbed - highly lipid soluble - irreversible binding
what do you give for OD
atropine (for antimuscarinic effects) and pralidoxime (acetylcholinesterase reactivator)
anticholinergics antagonize the effects of Ach at ____ receptors
muscarinic
muscarinic receptors are located
heart, salivary glands, smooth muscle GI and Gu tracts
anticholinergics MOA
competitive antagonists. compete with Ach at the cholinergic/muscarinic receptors
m1
CNS and stomach
m2
lungs and heart
m3
CNS , airway, smooth muscle, glandular tissue
m4 and m5
CNS
m3 causes
bronchodilation
which drug causes mydriasis and cycloplegia
glyco
which anticholinergic drug causes most sedation
scop
which anticholinergic has an increased incidence of memory deficits
atropine
delated arousal in first 30 min after cessation of anestheisa in patients reversed with
atropine/neostigmine
which anticholinergics cross the placenta
atropine and scop
which is the best antisialogogue
scop > glco > atropine
which has a longer DOA - scop or glyco
glyco
how does atropine treat intra op bradycardia
blocks the effects of ACh on the SA node
overdose symptoms of anticholinergics
anti-rest and digest. dry mouth, increased temp, dry and flushed skin skeletal weakness, orthostatic hypotension, fatal events
treatment for OD of anti-cholinergic
physo - may need to repeat dose since it Is metabolized rapidly
sugar has a ___ center and ____ exterior
hydrophobic, hydrophilic
sugga is not recommended for use in
severe renal impairment
use secondary contraception for ___ post suggamedex
one week
